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Herpes, Genital
Cecilia M. Kipnis, MD
image BASICS
DESCRIPTION
  • Chronic, recurrent infection of any area innervated by the sacral ganglia
  • Due to herpes simplex virus (HSV) type 1 or 2
  • HSV-1 causes anogenital and orolabial lesions.
  • HSV-2 causes anogenital lesions.
  • Primary episode: occurs in the absence of preexisting antibodies to HSV-1 or HSV-2 (may be asymptomatic)
  • 1st episode nonprimary: initial genital eruption (likely due to HSV-2); preexisting antibodies to HSV-1 are present.
  • Reactivation: recurrent episodes
  • Synonym(s): herpes genitalis
EPIDEMIOLOGY
  • Predominant age: 15 to 65 years; cases increase with age due to cumulative effect
  • Predominant sex: female > male
  • Predominant race: non-Hispanic blacks
Incidence
>700,000 new cases per year
Prevalence
  • 50-70% in developed countries, approaches 100% in developing countries (1)
  • Overall prevalence of HSV-2 is 10-40% in the general population and up to 60-95% in the HIV-positive population (1).
  • Up to 90% of seropositive persons do not have formal diagnosis.
  • >50 million are infected with HSV-2 in the United States.
ETIOLOGY AND PATHOPHYSIOLOGY
  • HSV is a double-stranded DNA virus of the Herpetoviridae family (1).
  • Spread via genital-to-genital contact, oral-to-genital contact, and via maternal-fetal transmission. Viral shedding continues in the absence of lesions (2).
  • Incubation is 2 to 12 days after exposure.
RISK FACTORS
  • Risk increases with age, number of lifetime partners, history of sexually transmitted infections (STIs), sexual encounters before the age of 17 years, and partner with HSV-1 or HSV-2.
  • Infection with HSV-1 increases the risk of being infected with HSV-2 by 3-fold.
  • Immunosuppression, fever, stress, and trauma increases risk of reactivation.
COMMONLY ASSOCIATED CONDITIONS
Syphilis, HIV, chlamydia, gonorrhea, and other STIs
image DIAGNOSIS
PHYSICAL EXAM
  • Impossible to differentiate primary, 1st episode nonprimary, recurrent disease, or type of virus (HSV-1 or HSV-2) based on symptoms or exam
  • Lesions occur in “boxer short” distribution and within anus, vagina, and on cervix.
  • Lesion may appear as papular, vesicular, pustular, ulcerated, or crusted; can be in various stages.
  • Inguinal lymphadenopathy
  • Extragenital manifestations include meningitis, recurrent meningitis (Mollaret syndrome), sacral radiculitis/paresthesias, encephalitis, transverse myelitis, and hepatitis
Pediatric Considerations
  • Neonatal infection occurs in 20 to 50/100,000 live births; 80% of infections result from asymptomatic maternal viral shedding during an undiagnosed primary infection in the 3rd trimester.
  • Transmission ranges from 30-50% if the primary episode is near time of delivery. High morbidity and mortality
  • Suspect sexual abuse with genital lesions in children
DIFFERENTIAL DIAGNOSIS
  • Primary syphilis
  • Chancroid
  • Herpes zoster
  • Ulcerative balanitis
  • Granuloma inguinale
  • Lymphogranuloma venereum
  • HIV
  • Cytomegalovirus; Epstein-Barr virus
  • Drug eruption
  • Trauma
  • Behçet syndrome
  • Neoplasia
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Viral isolation from lesion (swab or scraping)
    • Culture and PCR are preferred (3)[A].
    • Use Dacron or polyester-tipped swabs with plastic shafts (cotton tips/wood shafts inhibit viral growth and/or replication) (1).
    • Culture by unroofing vesicle to obtain fluid sample. Specificity >99%, sensitivity depends on sample: 52-93% for vesicle, 41-72% for ulcer, 19-30% for crusted lesion (1,3)
    • Culture requires timely transport of live virus to the laboratory in appropriate medium at 4°C.
    • PCR has the greatest sensitivity (98%) and specificity (>99%) but is also expensive and not readily available. It can increase detection rates by up to 70% (4). Used primarily for CSF (1)
  • Type-specific serologic assays
    • Western blot (gold standard) and type-specific IgG antibody (glycoprotein G) enzyme-linked immunosorbent assay (ELISA) are used to discriminate between HSV-1 and HSV-2 (3)[B].
    • Western blot is >97-99% sensitive and specific but labor intensive and not readily available (1,3).
    • ELISA is 81-100% sensitive and 93-100% specific (1).
    • Seroconversion occurs 10 days to 4 months after infection (3). Antibody testing is not necessary if a positive culture or PCR has been obtained.
    • IgM antibody testing is not useful because HSV IgM is often present with recurrent disease and does not distinguish new from old infection.
    • Screening with type-specific antibody in the general population is not recommended (3) but may be considered in
      • Asymptomatic patients with HIV infection
      • Discordant couples (one partner with known HSV, the other without)
image TREATMENT
GENERAL MEASURES
  • Cool compresses with aluminum acetate (Domeboro)
  • Ice packs to perineum, sitz baths, topical anesthetics
  • Analgesics, NSAIDs
MEDICATION
Antiviral medications should be started within 72 hours of onset of symptoms (including prodrome). If presentation is >72 hours, antivirals may be helpful if new lesions continue to form or patient is experiencing significant pain.
P.481

First Line
  • Acyclovir (4)[A]: the most studied antiviral in genital herpes. Decreases pain, duration of viral shedding, and time to full resolution
    • Primary episode
      • 400 mg PO TID for 7 to 10 days
      • 200 mg PO 5 times a day for 7 to 10 days
      • Longer if needed for incomplete healing
    • Episodic therapy
      • 200 mg 5 times per day for 5 days
      • 400 mg TID for 5 days
      • 800 mg BID for 5 days
      • 800 mg TID for 2 days
    • Daily suppression
      • 400 mg BID
    • Severe, complicated infections requiring IV therapy
      • 5 to 10 mg/kg/dose q8h until clinical improvement; switch to PO therapy to complete a 10-day course.
    • HIV infection: 400 mg PO 3 to 5 times per day until clinical resolution is attained
    • Precautions
      • Modify dose in renal insufficiency.
  • Valacyclovir (Valtrex) (4)[A]: prodrug of acyclovir, improved bioavailability, less frequent dosing
    • Primary episode
      • 1 g PO BID for 7 to 10 days
    • Episodic therapy
      • 500 mg PO BID for 3 to 5 days
      • 1 g PO daily for 5 days
    • Daily suppression
      • 500 mg PO daily
      • 1 g PO daily
  • Famciclovir (Famvir) (4)[A]
    • Primary episode
      • 250 mg PO TID for 7 to 10 days
    • Episodic therapy
      • 125 mg PO BID for 5 days
      • 1 g PO BID for 1 day
    • Daily suppression: 250 mg PO BID
Second Line
  • Used for acyclovir-resistant HSV
  • Foscarnet: 40 mg/kg/dose IV q8h in severe disease
    • Associated with significant toxicity
  • Cidofovir topical: 0.1-0.3% gel for 5 days
Pregnancy Considerations
ACOG Clinical Management Guidelines (4)[A],(5)[C]:
  • SCREENING: Pregnant women who test antibody negative for HSV-1 and HSV-2 should avoid sexual contact in the 3rd trimester if their partner is antibody positive.
  • SUPPRESSIVE THERAPY: Pregnant women with a history of genital herpes should be offered suppression treatment starting at 36 gestational weeks until delivery to decrease reactivation rate. Goal is to reduce the risk of neonatal infection and C-section. Recommended regimens to continue until delivery:
    • Acyclovir 400 mg PO TID
    • Valacyclovir 500 mg PO BID
  • Monitor for outbreaks during pregnancy and examine for any lesions at the onset of labor. C-section is recommended if prodromal symptoms or lesions are present at onset of labor to reduce neonatal transmission.
Pediatric Considerations
  • High-risk infants include those with active symptoms or lesions, those delivered vaginally with maternal lesions present, and those born during a primary maternal episode. Monitor closely, obtain diagnostic laboratory specimens (HSV PCR and ocular, nasal, anal, and oral cultures), and treat with acyclovir 20 mg/kg IV q8h for 10 to 14 days (4)[A].
  • Low-risk infants who are asymptomatic can be observed while obtaining serum HSV PCR and ocular, nasal, anal, and oral cultures.
  • Infants with possible HSV infection should be isolated from other neonates; maternal separation is not necessary and breastfeeding is not contraindicated.
image ONGOING CARE
GENERAL PREVENTION
  • Use barrier contraception, daily suppressive antiviral therapy, and avoid sexual contact when symptoms are present to decrease transmission.
  • Abstinence is the only means of complete protection.
FOLLOW-UP RECOMMENDATIONS
  • Avoid sexual contact when symptoms or lesions are present.
  • Alert partners of herpes status prior to sexual activity.
  • Concordant couples (i.e., both partners with the same type of herpes [HSV-1 or HSV-2]) may have sex without worry of triggering outbreaks.
Patient Monitoring
Test for other STIs if initial HSV infection
PATIENT EDUCATION
  • Herpes Resource Center: http://www.ashasexualhealth.org/stdsstis/herpes/
  • Warren T. The Good News About the Bad News: Herpes: Everything You Need to Know. Oakland, CA: New Harbinger Publications; 2009.
  • Centers for Disease Control and Prevention: http://www.cdc.gov/
PROGNOSIS
  • Resolution of signs/symptoms: 3 to 21 days
  • Average recurrence rate is one to four episodes per year (2).
  • Antivirals do not eliminate virus from body but can reduce transmission, shedding, and outbreaks.
Pediatric Considerations
Neonatal infection survival rates: localized >95%, CNS 85%, systemic 30%
REFERENCES
1. LeGoff J, Péré H, Bélec L. Diagnosis of genital herpes simplex virus infection in the clinical laboratory. Virol J. 2014;11:83.
2. Hofstetter AM, Rosenthal SL, Stanberry LR. Current thinking on genital herpes. Curr Opin Infect Dis. 2014;27(1):75-83.
3. Geretti AM. Genital herpes. Sex Transm Infect. 2006;82(Suppl 4):iv31-iv34.
4. Centers for Disease Control and Prevention. 2010 sexually transmitted diseases treatment guidelines. http://www.cdc.gov/std/treatment/2010/. Accessed 2014.
5. ACOG Committee on Practice Bulletins. ACOG practice bulletin. Clinical management guidelines for obstetrician-gynecologists. No. 82 June 2007. Management of herpes in pregnancy. Obstet Gynecol. 2007;109(6):1489-1498.
Additional Reading
&NA;
  • Money D, Steben M. SOGC clinical practice guidelines: guidelines for the management of herpes simplex virus in pregnancy. Number 208, June 2008. Int J Gynaecol Obstet. 2009;104(2):167-171.
  • Tavares F, Cheuvart B, Heineman T, et al. Metaanalysis of pregnancy outcomes in pooled randomized trials on a prophylactic adjuvanted glycoprotein D subunit herpes simplex virus vaccine. Vaccine. 2013;31(13):1759-1764.
  • Tobian AA, Grabowski MK, Serwadda D, et al. Reactivation of herpes simplex virus type 2 after initiation of antiretroviral therapy. J Infect Dis. 2013;208(5):839-846.
See Also
&NA;
Algorithm: Genital Ulcers
Codes
&NA;
ICD10
  • A60.00 Herpesviral infection of urogenital system, unspecified
  • A60.04 Herpesviral vulvovaginitis
  • A60.09 Herpesviral infection of other urogenital tract
Clinical Pearls
&NA;
  • Genital herpes infections can be caused by HSV-1 and HSV-2.
  • Many seropositive individuals are unaware that they are infected.
  • Most primary episodes are asymptomatic.
  • Viral shedding occurs in the absence of lesions.